Nimodipine Protects Vascular and Cognitive Function in an Animal Model of Cerebral Small Vessel Disease

BACKGROUND: Cerebral small vessel disease is a common cause of vascular cognitive impairment and dementia. There is an urgent need for preventative treatments for vascular cognitive impairment and dementia, and reducing vascular dysfunction may provide a therapeutic route. Here, we investigate whether the chronic administration of nimodipine, a central nervous system-selective dihydropyridine calcium channel blocking agent, protects vascular, metabolic, and cognitive function in an animal model of cerebral small vessel disease, the spontaneously hypertensive stroke-prone rat. METHODS: Male spontaneously hypertensive stroke-prone rats were randomly allocated to receive either a placebo (n=24) or nimodipine (n=24) diet between 3 and 6 months of age. Animals were examined daily for any neurological deficits, and vascular function was assessed in terms of neurovascular and neurometabolic coupling at 3 and 6 months of age, and cerebrovascular reactivity at 6 months of age. Cognitive function was evaluated using the novel object recognition test at 6 months of age. RESULTS: Six untreated control animals were terminated prematurely due to strokes, including one due to seizure, but no treated animals experienced strokes and so had a higher survival (P=0.0088). Vascular function was significantly impaired with disease progression, but nimodipine treatment partially preserved neurovascular coupling and neurometabolic coupling, indicated by larger (P<0.001) and more prompt responses (P<0.01), and less habituation upon repeated stimulation (P<0.01). Also, animals treated with nimodipine showed greater cerebrovascular reactivity, indicated by larger dilation of arterioles (P=0.015) and an increase in blood flow velocity (P=0.001). This protection of vascular and metabolic function achieved by nimodipine treatment was associated with better cognitive function (P<0.001) in the treated animals. CONCLUSIONS: Chronic treatment with nimodipine protects from strokes, and vascular and cognitive deficits in spontaneously hypertensive stroke-prone rat. Nimodipine may provide an effective preventive treatment for stroke and cognitive decline in cerebral small vessel disease.

During her tenure as interim chair, Dr. Addis led the OB department through tremendous growth of faculty, increase in P&T of current faculty and increase in research, publications and development of OB faculty. "She is an exceptional role model for leadership. Despite how busy she was, she made the time to push me toward my own development as a leader, encouraging and supporting my application to leadership programs both locally and nationally. Dr. Addis has had a tremendous impact on the success of many. She has coached numerous faculty and residents through professional growth and continues to be intentional about creating opportunities for others."

Ilana Addis, MD -Associate Professor (Clinical Scholar), OBGYN
"Dr. Czuzak has mastered the tricky balance of providing help when needed, but also trusting mentees to get the job done after setting expectations. She acts as a source of feedback, needed when developing new courses. She also helped me understand the administrative structure of the college, the roles of our different committees, and by introducing me to key faculty and staff who teach in our pre-clerkship curriculum and who work in admissions and curriculum development. Her mentorship has allowed me to thrive as a junior faculty here at Uarizona College of Medicine-Tucson."

Maria Czuzak, PhD -Associate Professor (Clinical Scholar), CMM
-"distinct superpowers is seeking out the uniqueness and potential in others." -"Listener. He picks up on things that don't necessarily fit with the status quo, but will improve the individual or the system, and actively looks for ways to nurture and grow these new ideas." -"The ability to see things from my point of view, while also understanding my ultimate goals and then using his experience, knowledge, and seniority to help me, epitomizes an excellent mentor." -"Our world needs more mentors like Dr. Ditillo."

Michael Ditillo, DO -Clinical Assistant Professor (Clinical Series), Surgery
His letters of nomination spoke to helping those he mentors find balance between academic and clinical responsibilities contributing to their wellbeing and success as well as always modeling what it means to be an excellent clinical partner. "He is the mentor I aim to be."

Bellal Joseph, MD -Professor (Tenured), Surgery
Her nomination letter was beautiful. Let me paraphrase a little here, "She mentors by example, modeling exemplary patient care and has helped me directly navigate more challenging resident advising concerns with grace and kindness. This mentorship has led to great satisfaction with my early career, helping me to avoid burnout and be as successful as possible in my new roles. She helps support my passion and enthusiasm for my work, making it easier to continue through the common struggles of our calling in medicine.."

Elizabeth Kyle Meehan, MD -Assistant Professor (Clinical Scholar), FCM
"Her coaching and feedback have been instrumental in the development of my leadership skills, including the art of engaging others, developing networks, and optimizing negotiation. Equally important, she has helped me to overcome imposter syndrome, a critical barrier to career advancement for many academic physicians who are underrepresented in medicine. She is an incredible example of humble yet powerful leadership, always looking for what she can do to promote the advancement of others. I aspire to be the type of mentor that she has been to so many and will consider it a success if I am able to accomplish a fraction of that."

Victoria Murrain, DO -Associate Professor (Clinical Scholar), FCM
In his nomination letter, "Dr. Sanders is a steadfast advocate for a better medical system, including his work in medical ethics. In addition to the training, coaching, and introducing he has done as a mentor, he is an incredible role model. His support and belief in me have made lasting effects in my career trajectory and life in general."

Arthur Sanders, MD -Professor (Tenured), Emergency Medicine
"Upon observing Dr. Shroff's leadership daily for the past several years, it is apparent that I am not alone in benefiting from her positive influence. Patient, staff, and colleagues alike have commented on the level of professionalism, dedication, and care that she demonstrates daily. While she has many talents, perhaps the most remarkable are her dedication to mentorship and passion for accomplishment through teamwork. Dr. Shroff's mentorship and leadership style has had a major, positive impact on my career. I am so grateful for the opportunities she has given me and or the important lessons she has taught me."

Rachna Shroff, MD -Associate Professor (Tenure Eligible), Medicine
"What's truly special about the mentorship Dr. Smith has provided to me is not any one individual thing that she has done, it is the sustained duration and dedication of her mentorship and the number of opportunities she has afforded to me. She is a pleasure to work with, she is grounded and able to share in the full range of experience involved in psychiatry, education, mentorship and life. With her humanity, clinical work, professionalism, ethical conduct, educational activity,